Categories
Internal Medicine Renal System

Nephrolithiasis

Renal calculi caused by a disruption in the balance between solubility and precipitation of salts in the urinary tract and in the kidneys.

Renal calculi caused by a disruption in the balance between solubility and precipitation of salts in the urinary tract and in the kidneys.

  • #2 M/C chronic kidney condition (after hypertension)

Etiology

Fundamental cause for all stones is supersaturation of urine with respect to the stone components; factors affecting solubility include urine volume, pH, and total solute excretion.

Low fluid intake

Single most important determinant of stone formation is low fluid intake. A low fluid intake results in the production of concentrated urine, causing supersaturation and crystallisation of stone–forming compounds. In addition, low urine flow rates favour crystal deposition on the urothelium.

Stone types:

  • Calcium oxalate/mix (75%)
  • Calcium phosphate (brushite) (5%)
  • Uric acid (5-15%)
  • Struvite (Mg ammonium phosphate) (10-20%)
  • Cystine (1%)
Type of stones. Light microscopy of urine crystals
Type of stones. Light microscopy of urine crystals: (A) Hexagonal cystine crystal (200X); (B) coffin-lid shaped struvite crystals (200X); (C) pyramid-shaped calcium oxalate dehydrate crystals (200X); (D) dumbbell-shaped calcium oxalate monohydrate crystal (400X); (E) rectangular uric acid crystals (400X); and (F) rhomboidal uric acid crystals (400X). | Asplin JR. Evaluation of the kidney stone patient. Semin Nephrol. 2008;28:99–110.

Calcium stones:

About 80% of stones are calcium based, predominantly either calcium oxalate (70%) or calcium phosphate (10%)
  • Hypercalciuria
  • High salt diet
  • Low urine volume
  • Hypocitraturia

Hypercalciuria:

High urine calcium is the single most common abnormality of urine chemistry in recurrent stone formers, but until recently the relative contributions of altered gut absorption, bone turnover, and renal handling were poorly understood.
  • Often occurs with diseases associated with hypercalcemia:
    • Hyperparathyroidism
    • Malignancy
    • Sarcoidosis
    • Vitamin D excess
    • Idiopathic hypercalciuria
    • Dent’s disease: X-linked disorder characterized by hypercalciuria, nephrocalcinosis, and the development of renal failure
  • Calcium phosphate stones: Alkaline urine
Model of idiopathic hypercalciuria
Model of idiopathic hypercalciuria. | Han, H., Segal, A. M., Seifter, J. L., & Dwyer, J. T. (2015). Nutritional Management of Kidney Stones (Nephrolithiasis). Clinical nutrition research, 4(3), 137–152. https://doi.org/10.7762/cnr.2015.4.3.137

Calcium oxalate stone:

Hyperoxaluria, which occurs due to bowel disease (enteric hyperoxaluria) and genetic disorders of oxalate metabolism (primary hyperoxaluria)
  • Low calcium intake
  • High animal protein intake: Animal protein (meat, poultry, fish) is metabolised to oxalate and uric acid
  • Endogenous metabolism of glycine, hydroxyproline and ascorbic acid.

Uric acid stones:

Pure uric acid calculi are radiolucent on plain radiographs but visible on ultrasonography or computerized tomography (CT).
  • Hyperuricosuria: History of gout (15-20%)
  • Diet rich in animal protein: High purine content, which produces uric acid in its catabolism, may increase the risk of uric acid stone formation
  • Urinary pH < 5.5 (main determinant for uric acid stones)

Cystine stones:

These stones tend to form only in patients with cystinuria an autosomal recessive disorder accounting for only 1% cases of nephrolithiasis
  • Cystinuria:
    • Nephrolithiasis (only clinical manifestation): Arises as a result of abnormal renal tubule transport which in turn leads to large amounts of urinary cystine excretion.
    • Stones begin to form in the 1st to 4th decades of life and tend to be large, multiple and bilateral.
    • Urinary tract infection and obstruction are common, as is stone recurrence every 1-4 years.
    • Typical hexagonal crystals in the urine

Struvite stones or triple phosphate stones or infection stones.

Normal urine is undersaturated with ammonium phosphate; struvite stone formation occurs only when ammonia production is increased and the urine pH is elevated, which decreases the solubility of phosphate. Bacterial urease is essential for the development of struvite stones because it leads to an elevation in ammonium, carbonate and urinary pH all at the same time. In this setting phosphate combines with ammonium, magnesium and carbonate to form a stone composed of magnesium ammonium phosphate (struvite) and calcium carbonate-apatite.
  • Urea breakdown by urease:
    • Urea → 2NH3 + CO2
  • Ammonia produced in reaction combines with water:
    • NH3 + H2O → NH4+ + OH
  • Upper urinary tract infections with urease-producing bacteria:
    • Proteus and Klebsiella (M/C)

They are typically very large and may be so large as to fill the renal pelvis (forming a “Staghorn calculus”). Their growth is rapid and they often grow back after surgical removal because infected fragments of stone have been left behind.


Pathophysiology

Renal stone formation is a biological process that involves physicochemical changes and supersaturation of urine. Stone growth starts with the formation of crystals in supersaturated urine which then adhere to the urothelium, thus creating the nidus for subsequent stone growth.

Mircroscopic & macroscopic location of stones:

Kidney stone locations in the urinary system
Kidney stone locations in the urinary system. | (A) Zahid I. H., Bawazir A. S., Naser R. Plant based native therapy for the treatment of Kidney stones in Aurangabad (M.S) Journal of Pharmacognosy and Phytochemistry. 2013;1(6):189–193. | (B) Evan A. P. Physiopathology and Etiology of stone formation in the kidney and the urinary tract. Pediatric Nephrology. 2010;25(5):831–841. doi: 10.1007/s00467-009-1116-y.

Mechanisms of stone formation:

  • Free particle mechanism: Crystals form ‘Randall’s plugs’ in the tubule
  • Fixed particle mechanism: Stones grow on Randall’s plaques (foundation of calcium phosphate on renal papillary surface)
Macroscopic and microscopic morphology of human kidneys and location of stones
Macroscopic and microscopic morphology of human kidneys and location of stones: a) According to the fixed-particle mechanism, stones begin as depositions of calcium phosphate (CaP) in the interstitium (apatite), grow outwards reaching the renal papillary surface, become exposed to the pelvic urine and establish a nucleus for the deposition of calcium oxalate (CaOx), leading to the formation of CaOx stones attached to a CaP base, known as Randall’s plaques. b) By contrast, in the free-particle mechanism, for example, CaP, uric acid or cystine crystals form in the renal tubules, move with the urine, aggregate and plug the terminal collecting ducts. These plugs, called Randall’s plugs or lesions, are exposed to the pelvic urine. Deposition of CaOx crystals on the CaP plugs leads to the formation of CaOx kidney stones.
Schematic representation of the various events of kidney stone formation
Schematic representation of the various events of kidney stone formation. | Alelign, T., & Petros, B. (2018). Kidney Stone Disease: An Update on Current Concepts. Advances in urology, 2018, 3068365. https://doi.org/10.1155/2018/3068365

Presentation

Non-obstructing kidney stones produce no symptoms or signs apart from hematuria. All symptoms when present, are relieved quite abruptly when the stone moves out of the ureter into the bladder and passes.

Acute renal colic:

M/C presentation
  • Intermittent colicky flank pain that may radiate to the lower abdomen or groin
  • Pain not affected by change in postition
  • Associated with nausea & vomiting
  • Associated hematuria (macroscopic > microscopic)
Diagram showing the typical location of renal colic, below the rib cage to just above the pelvis
Diagram showing the typical location of renal colic, below the rib cage to just above the pelvis | By NIH – Taken from http://kidney.niddk.nih.gov/spanish/pubs/stones_ez/index.htm, Public Domain, https://commons.wikimedia.org/w/index.php?curid=1148434

Lower urinary tract symptoms (LUTS):

If the stone lodged at uretero-vesical junction,
  • Dysuria
  • Urgency & frequency

Pediatric nephrolithiasis:

Symptoms in children can be similar
  • Hematuria
  • Generalized abdominal pain
  • Urinary tract infection (UTI)

Recurrence:

Recurrence usually occurs after a first stone, in the absence of preventive treatment. Probability of recurrence for idiopathic calcium stones after the initial event is 40–50% at 5 years and 50–60% by 10 years. The recurrence rate for stones associated with systemic diseases such as cystinuria or primary hyperparathyroidism is often higher.

Diagnosis

Urine analysis (UA) with microscopy:

  • Gross blood ± microscopic hematuria
  • ± Leukocyte esterase
  • ± Nitrites
  • + RBC, WBC (hematuria)
  • Urinary stone crystals
Struvite (magnesium ammonium phosphate) crystals found microscopically in a urinalysis of a dog with a bladder infection
Struvite (magnesium ammonium phosphate) crystals found microscopically in a urinalysis of a dog with a bladder infection. | By Joel Mills – Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=1607945

24-hour urine collection & analysis:

Best way to evaluate stone risk
  • Measure urine calcium, oxalate, uric acid, pH, volume, creatinine and citrate.

Kidney, ureter and bladder (KUB) film

Visualize calcium-containing stones in kidney/ureter, including struvite stones, but uric acid or other purine stones may be radiolucent, and cystine stones often visualize poorly as well

Renal ultrasound:

Ideal initial imaging study of choice in pediatric and pregnant patients to avoid radiation.

Non-contrast helical CT:

Accurately visualize size & location of stones in the urinary tract
Axial CT scan of abdomen without contrast, showing a 3-mm stone (marked by an arrow) in the left proximal ureter
Axial CT scan of abdomen without contrast, showing a 3-mm stone (marked by an arrow) in the left proximal ureter | By James Heilman, MD – Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=16263157

Differential diagnosis:

Other conditions causing flank pain and hematuria
  • Papillary necrosis with passage of a sloughed papilla
  • Renal emboli
  • Renal tumor
  • Urinary tract infection (UTI)

Management

Observation:

Initial management of stones less than 5 mm in patients without anatomic abnormalities of the urinary tract is watchful waiting, to allow time for stone passage. Pain can be controlled with use of NSAIDS or narcotic agents. Presence of any signs of urinary tract infection, inability to take oral fluids, or obstruction of a single functioning kidney requires hospitalization and active management.

Dietary management:

All patients in whom further management is appropriate should receive dietary and lifestyle advice. In temperate climates, a fluid intake of at least two litres a day halves recurrence rates. A diet high in fruit and vegetables is recommended because the high potassium content promotes urinary citrate excretion. These foods are also a source of phytates which, like citrate, increase calcium salt solubility. An adequate calcium intake, with restricted animal protein, reduces urine oxalate. A limited salt and sugar intake is also advised. Where possible, an underlying disorder predisposing to stone formation should be identified and treated.
Abnormalities of urine chemistry that increase risk of kidney stones and warrant further investigation
Abnormalities of urine chemistry that increase risk of kidney stones and warrant further investigation | PH = primary hyperoxaluria | Dawson, C. H., & Tomson, C. R. (2012). Kidney stone disease: pathophysiology, investigation and medical treatment. Clinical medicine (London, England), 12(5), 467–471. https://doi.org/10.7861/clinmedicine.12-5-467

Medical management:

Citrate is the most common inhibitor of crystal formation and urinary pH is very important for preventing or treating different types of stones.
  • Calcium stones:
    • Thiazide diuretics (lead to increased serum calcium levels and reduced urine calcium levels)
  • Uric acid stones:
    • Urine alkalinization
    • Allopurinol (xanthine oxidase inhibitor)
  • Cysteine stones:
    • Penicillamine & Tiopronin
    • Urinary alkalinization
  • Struvite stones: Surgical removal only option
    • Antibiotic therapy (slow stone growth).
    • Low sodium diet

Urologic management:

Surgical treatment required for 10–20% of symptomatic stones that fail to pass spontaneously. The appropriate modality for a given case depends on the size, location and type of stone; the presence of anatomical abnormalities or infection also may influence the choice.
Algorithm for the most common approaches to surgical treatment of kidney stones
Algorithm for the most common approaches to surgical treatment of kidney stones: The decision of which surgical strategy to use is dictated by the location of the stone (with lower-pole stones being more difficult to treat), stone size and stone density. | Khan, S. R., Pearle, M. S., Robertson, W. G., Gambaro, G., Canales, B. K., Doizi, S., Traxer, O., & Tiselius, H. G. (2016). Kidney stones. Nature reviews. Disease primers, 2, 16008. https://doi.org/10.1038/nrdp.2016.8

Extra-corporeal shock wave lithotripsy (ESWL):

Uses sound waves to fragment stones into small pieces that can be easily passed, is effective for most stones less than 2 cm in size, although cystine stones and phosphate stones may be resistant to fragmentation.
Extracorporeal shock wave lithotripsy (ESWL)
Extracorporeal shock wave lithotripsy (ESWL). | Han, H., Segal, A. M., Seifter, J. L., & Dwyer, J. T. (2015). Nutritional Management of Kidney Stones (Nephrolithiasis). Clinical nutrition research, 4(3), 137–152. https://doi.org/10.7762/cnr.2015.4.3.137

Percutaneous nephrolithotomy (PCNL):

Larger stones, particularly those composed of cystine or struvite, can be approached via percutaneous access through a small flank incision, allowing direct visualization and intracorporeal lithotripsy for stone disruption, and removal of fragments.

Ureteroscopic management:

Useful for stones in ureter and renal pelvis, and may be used with laser lithotripsy as well.

Open ureterolithotomy:


Summary

Kidney stones
Khan, S. R., Pearle, M. S., Robertson, W. G., Gambaro, G., Canales, B. K., Doizi, S., Traxer, O. and Tiselius, H.-G. (2016) ‘Kidney stones’, Nature Reviews Disease Primers. Macmillan Publishers Limited, 2, p. 16008. Available at: http://dx.doi.org/10.1038/nrdp.2016.8.

Leave a Reply